Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia

TY - JOUR

T1 - Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia

AU - Gudbrandsdottir, Sif

AU - Brimnes, Marie

AU - Køllgaard, Tania

AU - Hasselbalch, Hans C

AU - Nielsen, Claus H

N1 - © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2018/1

Y1 - 2018/1

N2 - Objective: To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM). Methods: Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell-surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry. Results: PBMCs from ITP patients at baseline contained a lower proportion of IL-10+ B cells (P <.01) and IL-6+ B cells (P <.01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5+ B cells increased (P <.01) and CD27+ memory B cells decreased (P <.05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27+ B cells (R = −0.71; P <.05). Conclusion: Both treatment regimens normalized the frequencies of cytokine-producing B cells. The additional increase in CD5+ B cells after RTX+DXM is compatible with induction of Bregs.

AB - Objective: To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM). Methods: Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell-surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry. Results: PBMCs from ITP patients at baseline contained a lower proportion of IL-10+ B cells (P <.01) and IL-6+ B cells (P <.01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5+ B cells increased (P <.01) and CD27+ memory B cells decreased (P <.05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27+ B cells (R = −0.71; P <.05). Conclusion: Both treatment regimens normalized the frequencies of cytokine-producing B cells. The additional increase in CD5+ B cells after RTX+DXM is compatible with induction of Bregs.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Autoantibodies/blood

KW - B-Lymphocyte Subsets/drug effects

KW - B-Lymphocytes, Regulatory/drug effects

KW - Biomarkers

KW - Case-Control Studies

KW - Cytokines/metabolism

KW - Dexamethasone/pharmacology

KW - Female

KW - Humans

KW - Immunologic Factors/pharmacology

KW - Immunophenotyping

KW - Lymphocyte Depletion

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Platelet Count

KW - Purpura, Thrombocytopenic, Idiopathic/diagnosis

KW - Rituximab/pharmacology

KW - Young Adult

U2 - 10.1111/ejh.12978

DO - 10.1111/ejh.12978

M3 - Journal article

C2 - 28960473

SN - 0902-4441

VL - 100

SP - 45

EP - 52

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 1

ER -